Gene therapy using non-viral peptide vector in a canine systemic lupus erythematosus model

• Published in: Veterinary immunology and immunopathology Vol. 103; no. 3; pp. 223 - 233
• Main Authors: Choi, Eun-Wha, Shin, Il-Seob, Youn, Hwa-young, Kim, Dae-Yong, Lee, Hang, Chae, Young-Jin, Lee, Chang-Woo
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 10.02.2005
• Subjects: Amino Acid Sequence; animal disease models; Animals; Antibodies, Antinuclear - immunology; Antigens, CD; Antigens, Differentiation - genetics; Antigens, Differentiation - immunology; Autoantibodies - immunology; Costimulation; Creatinine - urine; CTLA-4; CTLA-4 Antigen; Cytomegalovirus; Dog; Dog Diseases - genetics; Dog Diseases - immunology; Dog Diseases - pathology; Dog Diseases - therapy; Dogs; Female; Fluorescent Antibody Technique; gene therapy; genes; Genetic Therapy - methods; genetic vectors; Genetic Vectors - genetics; Histocytochemistry; immune response; Immunoglobulin Constant Regions - genetics; lupus erythematosus; Lupus Erythematosus, Systemic - genetics; Lupus Erythematosus, Systemic - immunology; Lupus Erythematosus, Systemic - pathology; Lupus Erythematosus, Systemic - therapy; Male; Molecular Sequence Data; Non-viral peptide vector; nucleotide sequences; peptides; promoter regions; Protein Structure, Tertiary; Proteinuria - immunology; Rats; Rats, Sprague-Dawley; symptoms; Systemic lupus erythematosus; Transcription, Genetic; CTLA-4; Systemic lupus erythematosus; Costimulation; Dog; Non-viral peptide vector
• ISSN: 0165-2427; 1873-2534
• DOI: 10.1016/j.vetimm.2004.09.027

Although viral vectors are commonly used for therapeutic gene delivery, their applications are limited due to their specific cell membrane receptor-mediated infection and host immune response. In the present study, we constructed a non-viral peptide vector and applied it in the treatment of experimentally induced systemic lupus erythematosus-like disease in dogs. For therapeutic gene construction, the extracellular domain of canine CTLA-4, and the CH2–CH3 domains of canine immunoglobulin alpha constant region were inserted between the cytomegalovirus promoter and poly-adenylation sequence of bovine growth hormone. The constructed therapeutic gene was ligated to the non-viral synthetic peptide vector and was applied to systemic lupus erythematosus-like disease induced dogs. After gene therapy, clinical signs of systemic lupus erythematosus were reduced dramatically: the anti-nuclear antibody titers and urine protein/creatinine ratios were recovered to normal values, and the skin regained its normal histological features. The peptide vector did not show either tissue specific tropism or host induced immune response.